Synlett 2008(10): 1459-1462  
DOI: 10.1055/s-2008-1077794
LETTER
© Georg Thieme Verlag Stuttgart · New York

A Convenient One-Pot Synthesis of 7-Trifluoromethyl-Substituted Imidazo[4,5-b]pyridines

Thomas Wesch, Viktor O. Iaroshenko, Ulrich Groth*
Department of Chemistry, University of Konstanz, Universitätsstraße 10, 78457 Konstanz, Germany
Fax: +49(7531)884155; e-Mail: ulrich.groth@uni-konstanz.de;
Further Information

Publication History

Received 19 February 2008
Publication Date:
16 May 2008 (online)

Abstract

This communication describes a practical and facile one-pot approach for the synthesis of 7-trifluoromethyl-substituted imidazo[4,5-b]pyridines by the reaction of in situ generated 5-aminoimidazole and a 1,3-CCC-biselectrophile.

    References and Notes

  • 1a Temple C. Rose JD. Comber RN. Rener GA. J. Med. Chem.  1987,  30:  1746 
  • 1b Cristalli G. Vittori S. Eleuteri A. Grifantini M. Volpini R. Lupidi G. Capolongo L. Pesenti E. J. Med. Chem.  1991,  34:  2226 
  • 2a Cristalli G. Vittori S. Eleuteri A. Volpini R. Camaioni E. Lupidi G. Mohmoud N. Belvilaqua F. Palu G. J. Med. Chem.  1995,  38:  4019 
  • 2b Cundy DJ. Holan G. Otaegui M. Simpson GW. Bioorg. Med. Chem. Lett.  1997,  7:  669 
  • 3 Temple C. J. Med. Chem.  1990,  33:  656 
  • 4 Bukoski L. Janowiec M. Pharmazie  1989,  44:  267 
  • 5a Mantlo NB. Chakravarty PK. Ondeyka DL. Siegl PKS. Chang RS. Lotti VJ. Faust KA. Chen T.-B. Schorn TW. Sweet CS. Emmert SE. Patchett AA. Greenlee WJ. J. Med. Chem.  1991,  34:  2922 
  • 5b Bavetsias V. Sun C. Bouloc N. Reynisson J. Workman P. Linardopoulos S. McDonald E. Bioorg. Med. Chem. Lett.  2007,  17:  6567 
  • 5c Chang LCW. von Frijtag Drabbe Künzel JK. Mulder-Krieger T. Westerhout J. Spangenberg T. Brussee J. Ijzerman AP. J. Med. Chem.  2007,  50:  828 
  • 5d Mladenova G. Lee-Ruff E. Tetrahedron Lett.  2007,  48:  2787 
  • 6a Lawhorn BG. Mehl RA. Begley TP. Org. Biomol. Chem.  2004,  2:  2538 
  • 6b Clayton R. Davis ML. Fraser W. Li W. Ramsden CA. Synlett  2002,  1483 
  • 6c Humphries MJ. Ramsden CA. Synthesis  1999,  985 
  • 7 Bhat B. Groziak MP. Leonard NJ. J. Am. Chem. Soc.  1990,  112:  4891 
  • 8a Bégué J.-P. Bonnet-Delpon D. In Chimie Bioorganique et Médicinale du Fluor   CNRS Édition; Paris: 2005. 
  • 8b Hiyama T. In Organofluorine Compounds, Chemistry and Applications   Springer; Berlin, Heidelberg: 2000. 
  • 9a McClinton MA. McClinton DA. Tetrahedron  1992,  48:  6555 
  • 9b Nowak I. Robins MJ. J. Org. Chem.  2007,  72:  2678 
  • 10a Ohkura H. Berbarasov DO. Soloshonok VA. Tetrahedron Lett.  2003,  44:  2417 
  • 11a Zanatta N. Amaral SS. Esteves-Souza A. Echevarria A. Brondani PB. Flores DC. Bonacorso HG. Flores AFC. Martins MAP. Synthesis  2006,  2305 
  • 11b Marins MAP. Pereira CMP. Zimmermann NEK. Cunico W. Moura S. Beck P. Zanatta N. Bonacorso HG. J. Fluorine Chem.  2003,  123:  261 ; and references cited therein
  • 11c Narsaiah B. Sivaprasad A. Venkataratnam RV. J. Fluorine Chem.  1994,  66:  47 
  • 11d Schlosser M. Volle J.-N. Leroux F. Schenk K. Eur. J. Org. Chem.  2002,  2913 
  • 11e Druzhinin SD. Balenkova ES. Nenajdenko VG. Tetrahedron  2007,  63:  7753 
  • 12a Krasovsky AL. Hartulyari AS. Nenajdenko VG. Balenkova ES. Synthesis  2002,  133 
  • 12b Krasovsky AL. Moiseev AM. Nenajdenko VG. Balenkova ES. Synthesis  2002,  901 
  • 13a Tamura K. Mizukami H. Maeda K. Watanabe H. Uneyama K. J. Org. Chem.  1993,  58:  32 
  • 13b Uneyama K. J. Fluorine Chem.  1999,  97:  11 
  • 14 Gaudry R. Org. Synth.  1955,  3:  436 
  • 15 Menge GA. J. Am. Chem. Soc.  1934,  56:  2197 
  • 16 Hosmane RS. Brunett FN. Albert MS. J. Org. Chem.  1984,  49:  1212 
  • 18 Volochnyuk DM. Pushechnikov AO. Krotko DG. Sibgatulin DA. Kovalyova SA. Tolmachev AA. Synthesis  2003,  1531 
  • 20a Al-Shaar AHM. Gilmour DW. Lythgoe DJ. McClenaghan I. Ramsden CA. J. Chem. Soc., Perkin Trans. 1  1992,  2779 
  • 20b Al-Shaar AHM. Chambers RK. Gilmour DW. Lythgoe DJ. McClenaghan I. Ramsden CA. J. Chem. Soc., Perkin Trans. 1  1992,  2789 
  • 20c Humphries MJ. Ramsden CA. Synlett  1995,  203 
  • 21 Linderman RJ. Jamois EA. J. Fluorine Chem.  1991,  53:  79 
  • 22a Pearson RG. J. Am. Chem. Soc.  1963,  85:  3533 
  • 22b Pearson RG. Parr RG. J. Am. Chem. Soc.  1983,  105:  7512 
  • 22c Ayers PW. Faraday Discuss.  2007,  135:  161 
17

General Procedure A solution of amine 2a-i (5 mmol) in dried CH2Cl2 (2,5 mL) was heated until reflux. After a period of 15 min ethyl N-(cyanomethyl)formimidate 1 (5 mmol, 560 mg) was added under N2 counterflow. The mixture was allowed to stir under reflux for 2 h. To the hot reaction mixture the 1,3-biselectrophile of type 4a-e (5 mmol) was added. The mixture was stirred for 8 h. Then it was cooled down to ambient temperature. The crude product was worked up through flash column chromatography to obtain the product as white needles.
Selected Data for 5o
1H NMR (400 MHz, CDCl3): δ = 3.79 (s, 3 H, OCH3), 5.47 (s, 2 H, CH2), 6.89 (m, 2 H, Ph), 7.33 (m, 2 H, Ph), 7.87 (s, 1 H, H-6), 8.31 (s, 1 H, H-2). 13C NMR (100 MHz, CDCl3): δ = 47.5 (OCH3), 55.3 (CH2), 111.5 (m, C-6), 122.3 (q, 1 J CF = 278 Hz, CF3), 121.6 (q, 1 J CF = 278 Hz, CF3), 114.4 (Ph), 126.6 (Ph), 130.1 (Ph), 160.4 (Ph), 129.7 (q, 2 J CF = 36 Hz, C-7), 133.6 (C-7a), 143.1 (q, 2 J CF = 35 Hz, C-5), 148.4 (C-3a), 148.6 (C-2). 19F NMR (376 MHz, CDCl3): δ =

-62.59, -66.55.

19

CCDC 683462 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.